A novel targeting modality to enhance adenoviral replication by vitamin D3 in androgen-independent human prostate cancer cells and tumors

Chia Ling Hsieh, Haiyen E. Zhau, Leland W K Chung, Ling Yang, Li Miao, Fang Yeung, Chinghai Kao, Hua Yang

研究成果: 雜誌貢獻文章同行評審

40 引文 斯高帕斯(Scopus)

摘要

We report the development of a novel replication-competent adenoviral vector, Ad-hOC-E1, containing a single bidirectional human osteocalcin (hOC) promoter to drive both the early viral E1A and E1B gene. This vector selectively replicated in OC-expressing but not non-OC-expressing cells, with viral replication enhanced at least 10-fold on vitamin D3 exposure. Both the artificial TATA-box and hOC promoter element in this bidirectional promoter construct were controlled by a common OC regulatory element which selectively activated OC expression in cells. The expression of E1A and E1B gene by Ad-hOC-E1 can be markedly induced by vitamin D3. Unlike Ad-sPSA-E1, an adenoviral vector with viral replication controlled by a strong super prostate-specific antigen (sPSA) promoter which only replicates in PSA-expressing cells with androgen receptor (AR), Ad-hOC-E1 retarded the growth of both androgen-dependent and androgen-independent prostate cancer cells irrespective of their basal level of AR and PSA expression. A single i.v. administration of 2 × 109 plaque-forming units of Ad-hOC-E1 inhibited the growth of previously established s.c. DU145 tumors (an AR- and PSA-negative cell line). Viral replication is highly enhanced by i.p. administration of vitamin D3. Ultimately, enhancing Ad-hOC-E1 viral replication by vitamin D3 may be used clinically to treat localized and osseous metastatic prostate cancer in men.
原文英語
頁(從 - 到)3084-3092
頁數9
期刊Cancer Research
62
發行號11
出版狀態已發佈 - 6月 1 2002
對外發佈

ASJC Scopus subject areas

  • 腫瘤科
  • 癌症研究

指紋

深入研究「A novel targeting modality to enhance adenoviral replication by vitamin D3 in androgen-independent human prostate cancer cells and tumors」主題。共同形成了獨特的指紋。

引用此